Biomaterials and Bionanotechnology

Cover
Biomaterials and Bionanotechnology
Copyright
Dedication
List of Contributors
About the Editor
1 Design of Materials and Product Specifications
	1.1 Introduction
	1.2 Objectives and Scope of Design of Materials and Product Specifications
	1.3 Pharmaceutical Product Specification
		1.3.1 Concepts and the Need
		1.3.2 The Rationale for Designing Specifications
		1.3.3 Associated Terminologies
		1.3.4 Types of Specifications
	1.4 Designing of Specification
		1.4.1 Guidelines for Designing Specification for Drug Substance/Drug Product
			1.4.1.1 Justification for Specification
			1.4.1.2 Pharmacopoeial Test and Evolving Methodology
		1.4.2 Guidelines for Designing Specification for Packaging Material
			1.4.2.1 Justification for Specification
			1.4.2.2 Pharmacopoeial Tests and Evolving Methodology
	1.5 Handling of Out-of-Specification
		1.5.1 Phase I Investigation
		1.5.2 Phase II Investigation
	1.6 Finished Pharmaceutical Product
		1.6.1 Regulatory Requirements
		1.6.2 Schematic Plan for Verification of Specification
		1.6.3 Labeling
		1.6.4 Shelf-Life and Storage
	1.7 Importance of Specification on Pharmaceutical Quality System
	1.8 Conclusion
	Abbreviations
	References
	Further reading
2 Engineered Mesenchymal Stem Cells as Nanocarriers for Cancer Therapy and Diagnosis
	2.1 Introduction
		2.1.1 Nanotechnology as an Emerging Platform in Cancer Disease Management
		2.1.2 Mesenchymal Stem Cells
		2.1.3 Human Mesenchymal Stem Cells
	2.2 Engineering Mesenchymal Stem Cells as a Novel Formulation Strategy in Cancer Treatment
		2.2.1 Nanoparticles Engineered Mesenchymal Stem Cells in Breast Cancer Management
		2.2.2 Lung Cancer
		2.2.3 Brain Cancer
		2.2.4 Bone Cancer
		2.2.5 Ovarian Cancer
		2.2.6 Other Mesenchymal Stem Cell Nanoparticles in Cancer Treatment
	2.3 What Future Holds for Multifunctional Stem Cell Platform?
	2.4 Conclusion and Future Prospects
	Abbreviations
	References
3 Guiding Factors and Surface Modification Strategies for Biomaterials in Pharmaceutical Product Development
	3.1 Introduction to Biomaterials: Concept and Understanding
	3.2 Surface Modification of Biomaterials: Role in Product Development
		3.2.1 Enhancement of Drug Loading
		3.2.2 Selective Targeting
		3.2.3 Enhanced Drug Delivery to the Brain
		3.2.4 Macrophage Targeting
		3.2.5 Enhanced Transdermal Delivery
		3.2.6 Enhancement of Drug Stability
		3.2.7 Reduction of Blood Toxicity
		3.2.8 Enhanced Uptake by Cancer and Inflamed Tissues
		3.2.9 Enhancement of Bioadhesion
		3.2.10 Increased Blood Plasma Half-Life
		3.2.11 Site-Selective Drug Release Through the Enteric Coating
		3.2.12 Multiple Drug Release via Layer-by-Layer Approach
	3.3 Strategies Employed in the Surface Modification of Biomaterials
		3.3.1 Plasma Polymerization
		3.3.2 Heparinization to Improve Blood Compatibility
			3.3.2.1 Ionic Binding of Heparin
			3.3.2.2 Covalent Binding of Heparin
			3.3.2.3 Physical Blending of Heparin for Controlled Release
		3.3.3 Peptide Functionalization
			3.3.3.1 Covalent Approach
			3.3.3.2 One-Step Functionalization
		3.3.4 Calcium Phosphate Deposition
		3.3.5 Thermal Spray Deposition
		3.3.6 Ion Beam Assisted Deposition
		3.3.7 Pulsed Laser Physical Vapor Deposition
		3.3.8 Microarc Oxidation
		3.3.9 Magnetron Sputtering Deposition
		3.3.10 Electrophoretic Deposition
		3.3.11 Electrochemical Deposition
		3.3.12 Sol–Gel Methods
		3.3.13 Hot Isostatic Pressing
		3.3.14 Biomimetic Coatings
	3.4 Future Remarks and Conclusion
	Abbreviations
	References
	Further Reading
4 Biomaterials for Sustained and Controlled Delivery of Small Drug Molecules
	4.1 Introduction
	4.2 Biomaterial Science and Biomaterials
		4.2.1 Purpose and Definition
		4.2.2 Requirements for Biomaterials
		4.2.3 Synthesis (Additive Manufacturing) and Properties of Biomaterials
			4.2.3.1 Physical Properties
			4.2.3.2 Chemical Properties
			4.2.3.3 Mechanical Properties
				4.2.3.3.1 Tensile and Shear Properties
		4.2.4 Types of Biomaterials
			4.2.4.1 Metals
			4.2.4.2 Polymers
			4.2.4.3 Ceramics and Glasses
			4.2.4.4 Composites
	4.3 Biomaterial Applications for Sustained and Controlled Release for Various Drug Delivery Systems
		4.3.1 Oral Drug Delivery
		4.3.2 Ocular Drug Delivery
		4.3.3 Drug Delivery to Ear
		4.3.4 Pulmonary Drug Delivery
		4.3.5 Transdermal Drug Delivery
		4.3.6 Central Nervous System Drug Delivery (Brain and Spine)
		4.3.7 Cardiovascular Drug Delivery
		4.3.8 Orthopedic Drug Delivery
		4.3.9 Injectable Drug Delivery
		4.3.10 Implantable Drug Delivery
		4.3.11 Drug Delivery for Wound Closure
		4.3.12 Localized Drug Targeting (Cancer and Immunotherapy)
	4.4 Advancements in Biomaterial Applications
		4.4.1 Smart Components: Stimuli-Responsive Biomaterials
			4.4.1.1 Different Stimuli-Responsive Biomaterials
				4.4.1.1.1 Physical Stimuli-Responsive Biomaterials
					4.4.1.1.1.1 Thermoresponsive Biomaterials
					4.4.1.1.1.2 Magnetic-Responsive Biomaterials
					4.4.1.1.1.3 Electrical-Responsive Biomaterials
					4.4.1.1.1.4 Light-Responsive Biomaterials
					4.4.1.1.1.5 Mechanical-Responsive Biomaterials
					4.4.1.1.1.6 Ultrasound-Responsive Biomaterials
				4.4.1.1.2 Chemical Stimuli-Responsive Biomaterials
					4.4.1.1.2.1 pH-Responsive Biomaterials
					4.4.1.1.2.2 Redox-Responsive Biomaterials
				4.4.1.1.3 Biological Stimuli-Responsive Biomaterials
					4.4.1.1.3.1 Different Biomolecular-Responsive Biomaterials
					4.4.1.1.3.2 Enzyme-Responsive Biomaterials
			4.4.1.2 Multiple Stimuli-Responsive Biomaterial Systems
			4.4.1.2.1 Dual Stimuli-Responsive Biomaterial Systems
			4.4.1.2.2 Tri Stimuli-Responsive Biomaterial Systems
		4.4.2 Intelligent Drug Delivery Systems
			4.4.2.1 Affinity-Based Drug Delivery Systems
				4.4.2.1.1 Recognition Molecular Systems
			4.4.2.2 Reservoir-Based Drug Delivery Systems
				4.4.2.2.1 Microfabrication
				4.4.2.2.2 Nanobiomaterials
					4.4.2.2.2.1 Carbon Nanotubes
					4.4.2.2.2.2 Nanofibrous Scaffolds
					4.4.2.2.2.3 DNA-Based Nanostructures
				4.4.2.2.3 Hydrogels
	4.5 Challenges in Using Biomaterials for Drug Delivery
		4.5.1 General Aspects
		4.5.2 Biological Events Upon Host–Biomaterial Interaction and Solutions
			4.5.2.1 Protein Adsorption
			4.5.2.2 Biocompatibility
			4.5.2.3 Hemocompatibility
			4.5.2.4 Bacterial Infection
			4.5.2.5 Biodegradation
		4.5.3 Examples of Smart Biomaterial Challenges and Toxicities
		4.5.4 Biological Assessment Tests
	4.6 Regulatory and Patent Aspect of Biomaterials Employed for Sustained and Controlled Delivery of Small Drug Molecule
	4.7 Future Prospects and Conclusion
	References
	Further reading
5 Biotechnology-Based Pharmaceutical Products
	5.1 Introduction
		5.1.1 Differences to be Considered for Biotechnology-Based Products in Comparison With Conventional Drugs
	5.2 Production Process for Biotechnology-Based Products
		5.2.1 Upstream Process
			5.2.1.1 Gene Cloning
			5.2.1.2 Recombinant Deoxyribonucleic Acid Technology
				5.2.1.2.1 Vectors
				5.2.1.2.2 Host Cells
			5.2.1.3 Deoxyribonucleic Acid Libraries
				5.2.1.3.1 Genomic Deoxyribonucleic Acid Libraries
				5.2.1.3.2 Complementary Deoxyribonucleic Acid Libraries
		5.2.2 Downstream Process
			5.2.2.1 Isolation and Purification of Biotechnology-Based Products
			5.2.2.2 Characterization of Biotechnology-Based Products
	5.3 Overview of Pharmacokinetics of Pharmaceutical Biotechnology-Based Products
		5.3.1 Absorption
		5.3.2 Distribution
		5.3.3 Metabolism and Excretion
		5.3.4 Approaches Used for Improving the Pharmacokinetic Profile of Biotechnology-Based Pharmaceutical Products
	5.4 Problems Associated With Biotechnology-Based Pharmaceutical Products
		5.4.1 Formulation Stability of Pharmaceutical Biotechnology-Based Products
			5.4.1.1 Chemical Degradation
			5.4.1.2 Physical Degradation
		5.4.2 Immunogenicity of Biotechnology-Based Pharmaceutical Products
		5.4.3 Ethical and Regulatory Concerns of Biotechnology
	5.5 Biotechnology-Based Products: Processing, Production, and Application Perspectives
		5.5.1 Antibiotics
		5.5.2 Hormones
			5.5.2.1 Insulin Hormone
			5.5.2.2 Human Growth Hormone
		5.5.3 Enzymes
		5.5.4 Blood Clotting Factors
		5.5.5 Cytokines
			5.5.5.1 Interferons
			5.5.5.2 Interleukins
		5.5.6 Monoclonal Antibodies
		5.5.7 Vaccines
	5.6 A Summary of Commercially Available Leading Biotechnology-Based Products
	5.7 Nanobiotechnology
	5.8 Gene Therapy
	5.9 Pharmacogenomics
	5.10 Stem Cell Therapy
	5.11 Conclusion
	Abbreviations
	References
	Further reading
6 Approaches to the Development of Implantable Therapeutic Systems
	6.1 Introduction
		6.1.1 Skin
		6.1.2 Implantable Drug Delivery System
	6.2 Biodegradable and Nonbiodegradable Implant Systems
		6.2.1 Nonbiodegradable Systems
			6.2.1.1 Polymers Used in Nonbiodegradable Systems
				6.2.1.1.1 Polyurethanes
				6.2.1.1.2 Silicone Rubber
				6.2.1.1.3 Poly(Ethylene Vinyl Acetate)
		6.2.2 Biodegradable Systems
			6.2.2.1 Polymers Used in Biodegradable Systems
				6.2.2.1.1 Polyglycolic Acid
				6.2.2.1.2 Polylactic Acid
				6.2.2.1.3 Poly(Lactic-co-Glycolic Acid)
				6.2.2.1.4 Polysaccharides
				6.2.2.1.5 Polycaprolactone
	6.3 Mechanism of Drug Release From an Implantable Drug Delivery System
		6.3.1 Diffusion-Controlled Release
		6.3.2 Chemically Controlled Release
			6.3.2.1 Bioerosion
			6.3.2.2 Pendant Chain
		6.3.3 Swelling Controlled Release
		6.3.4 Osmotically Controlled Release
		6.3.5 Magnetic Controlled Release
	6.4 Implantable Pump System
		6.4.1 Infusion Pumps
		6.4.2 Peristaltic Pumps
		6.4.3 Osmotic Pumps
		6.4.4 Positive Displacement Pumps
	6.5 Atypical Implantable Drug Delivery Systems
		6.5.1 Micro/Nanofabricated Implantable Drug Delivery Systems
		6.5.2 Ceramic Drug Delivery Systems
	6.6 Modeling of an Implantable Drug Delivery System
		6.6.1 Empirical Models
			6.6.1.1 Higuchi Model
			6.6.1.2 Ritger–Peppas Model
			6.6.1.3 Peppas–Sahlin Model
			6.6.1.4 Alfrey Model
			6.6.1.5 Zero-Order Model
		6.6.2 Mathematical Models
			6.6.2.1 Mathematical Models for Diffusion-Based Drug Delivery System
			6.6.2.2 Mathematical Models for Dissolution Based Drug Delivery System
			6.6.2.3 Mathematical Models for Erosion Based Drug Delivery System
				6.6.2.3.1 Hopfenberg’s Model
				6.6.2.3.2 Katzhendler Model
				6.6.2.3.3 Rothstein Model
	6.7 Approaches for Development of Implantable Therapeutic Systems
		6.7.1 Controlled Drug release by Diffusion
		6.7.2 Controlled Drug Release by Activation
		6.7.3 Lucentis in a New Vehicle
		6.7.4 Biosilicon Technology
		6.7.5 Replenish Mini Pump
		6.7.6 Encapsulated Cell Technology
	6.8 Manufacturing and Sterilization Protocols
		6.8.1 Coacervation Phase Separation
		6.8.2 Emulsion Phase Separation
		6.8.3 Spray Drying
		6.8.4 Air Suspension
		6.8.5 Solvent Extraction
		6.8.6 PRINT
	6.9 Benefits of Controlled Drug Administration via Implantation
	6.10 Commercially Available Advanced Implantable Devices
	6.11 Future Scope and Conclusion
	References
7 Nanotechnology in Tissue Engineering
	7.1 Tissue Engineering: An Overview
	7.2 Nanotechnology in Tissue Engineering
	7.3 Strategies Related to the Formation of Scaffolds
		7.3.1 Photolithography
		7.3.2 Templating
		7.3.3 Ionic Self-Complementary Peptide
		7.3.4 Bionanotubes/Lipid Tubules
		7.3.5 Miscellaneous
	7.4 Natural Materials–Based Tissue Engineering Nanoscaffold
		7.4.1 The Chitosan-Based Tissue Engineering Scaffold
		7.4.2 The Albumin-Based Tissue Engineering Scaffold
		7.4.3 The Alginate-Based Tissue Engineering Scaffold
		7.4.4 The Silica-Based Tissue Engineering Scaffold
	7.5 Synthetic Materials–Based Tissue Engineering Nanoscaffolds
		7.5.1 The Dendrimer-Based Tissue Engineering Scaffold
		7.5.2 Poly(Lactic Acid-co-Glycolic Acid)-Based Tissue Engineering Scaffold
		7.5.3 Polylactic Acid–Based Tissue Engineering Scaffold
		7.5.4 The Polyethylene Glycol–Based Tissue Engineering Scaffold
	7.6 Applications
		7.6.1 Nanotechnology in Cell Tissue Engineering
			7.6.1.1 Nanotechnology in Bone Cells Tissue Engineering
			7.6.1.2 Nanotechnology in Vascular Cells Tissue Engineering
			7.6.1.3 Nanotechnology in Hepatic Cells Tissue Engineering
			7.6.1.4 Nanotechnology for Stem Cell Engineering
		7.6.2 Nanotechnology-Based Tissue Engineering for Cell Labeling, Purification, Detection, and Suicide Bombing
	7.7 Recent Patents Overview
		7.7.1 Magnetic Pole Matrices
		7.7.2 Differentiable Human Mesenchymal Stem Cells
		7.7.3 Degradable Polyurethane Foams
		7.7.4 Multilayer Polymer Scaffolds
	7.8 Clinical Trial Status
	7.9 Conclusion
	Abbreviations
	References
	Further reading
8 Novel Therapeutic Approaches for the Treatment of Leishmaniasis
	8.1 Introduction
		8.1.1 The Causative Agent: Leishmania
		8.1.2 Life Cycle of Leishmania
		8.1.3 Clinical Manifestations
		8.1.4 Pathology
			8.1.4.1 Visceral Leishmaniasis (Kala-Azar)
			8.1.4.2 Post-Kala-Azar Dermal Leishmaniasis
			8.1.4.3 Disseminated Cutaneous Leishmaniasis
			8.1.4.4 Diffuse Cutaneous Leishmaniasis
			8.1.4.5 Mucocutaneous Leishmaniasis
	8.2 Diagnosis
		8.2.1 Parasitological Diagnosis
		8.2.2 Serological Diagnosis
		8.2.3 Molecular Diagnosis
		8.2.4 Antibody Detection Diagnostic Tests
	8.3 Currently Used Drugs for the Treatment of Leishmaniasis
		8.3.1 Antimonial Agents
		8.3.2 Pentamidine
		8.3.3 Amphotericin B
		8.3.4 Miltefosine
		8.3.5 Paromomycin
	8.4 Combined Therapy
	8.5 Other Drugs Used for Leishmaniasis
		8.5.1 Sitamaquine
		8.5.2 8-Aminoquinolines
		8.5.3 2-Substituted Quinolines
		8.5.4 Buparvaquone and Its Derivatives
	8.6 Macrophage-Targeted Drug Delivery Using Nanocarriers
		8.6.1 Liposomes
		8.6.2 Nanoparticles
		8.6.3 Nanodisks
		8.6.4 Niosomes
		8.6.5 Emulsions
		8.6.6 Carbon Nanotubes
		8.6.7 Transfersomes
		8.6.8 Other Drug Delivery Systems
	8.7 Prophylactic Vaccines for Leishmaniasis
		8.7.1 Leishmanization
		8.7.2 First-Generation Aspirant Vaccines
		8.7.3 Second-Generation Vaccines
		8.7.4 Immunochemotherapy and Therapeutic Vaccines
	8.8 Conclusion
	Abbreviations
	References
	Further reading
9 Up-to-Date Implications of Nanomaterials in Dental Science
	9.1 Introduction: Understanding Dentistry and Underlying Problems in Dental Therapy
	9.2 Medical Approaches to Resolve Dental Issues: Emergence of Nanotechnology in Dentistry
	9.3 Various Nanomaterials Used in Dentistry
		9.3.1 Chitosan Biopolymer-Based Formulations
		9.3.2 Gelatin-Based Nanoformulations
			9.3.2.1 Delivery of Fibroblast Growth Factor-2 in Dental Pulp Therapy via Gelatin Hydrogel
			9.3.2.2 Delivery of Hydroxyapatite in Remineralization of Tooth Enamel
		9.3.3 Poly(Lactide-co-Glycolic Acid)
		9.3.4 Liposomes
		9.3.5 Silver Nanoparticles
		9.3.6 Zinc Oxide Nanoparticles
		9.3.7 Titanium Dioxide Nanoparticles
		9.3.8 Nanoemulsion-Based Approach
		9.3.9 Nanoemulgel Approach in Dentistry
	9.4 Conclusion and Future Prospects
	Abbreviations
	References
10 Current Research Perspectives of Orthopedic Implant Materials
	10.1 Introduction
	10.2 History of Implant Materials
		10.2.1 The Early Era or the Foundation Period
		10.2.2 Trauma in the Postwar Era or the Premodern Era
	10.3 Development of Implant Materials Through Various Generations
		10.3.1 First Generation
			10.3.1.1 Metallic Materials
			10.3.1.2 Ceramic Materials
			10.3.1.3 Polymers
		10.3.2 Second Generation
		10.3.3 Third Generation
	10.4 Vital Properties for the Selection of Implant Material
		10.4.1 Bulk Properties
		10.4.2 Surface Properties
		10.4.3 Biocompatibility
	10.5 Implant Materials Used in Orthopedic
		10.5.1 Metals
		10.5.2 Polymers
		10.5.3 Ceramics
	10.6 Orthopedic Implant Manufacturing: Design and Development
		10.6.1 Design Process
		10.6.2 Feasibility
		10.6.3 Design
		10.6.4 Design Verification
		10.6.5 Manufacture
		10.6.6 Design Validation
		10.6.7 Design Transfer
		10.6.8 Design Changes
	10.7 Manufacturing Requirements for the Implant Materials
		10.7.1 Mechanical Properties
			10.7.1.1 Bulk Properties
			10.7.1.2 Surface Properties
		10.7.2 Nonmechanical Requirements
	10.8 Coating Technologies/Approaches for Orthopedic Implants
		10.8.1 Electrostatic Spray Deposition
		10.8.2 Fiber Laser Surface Engineering
	10.9 Tissue-Implant Responses
	10.10 Modeling Fracture Process in Orthopedic Implants
	10.11 Complications Associated With the Performance of the Implant Materials
		10.11.1 Sensitization, Irritation, and Intracutaneous (Intradermal) Reactivity
		10.11.2 Systemic Toxicity (Acute Toxicity) and Subacute and Subchronic Toxicity
		10.11.3 Genotoxicity
		10.11.4 Carcinogenicity
		10.11.5 Reproductive and Developmental Toxicity
	10.12 Current Trends in the 21st Century
		10.12.1 Titanium
		10.12.2 Aluminum Base Alloys
		10.12.3 Zirconia
		10.12.4 Cross-Linked Polyethylene
			10.12.4.1 Peroxide
			10.12.4.2 Moisture Cross-Linking
			10.12.4.3 Irradiation
	10.13 Regulatory Approvals and Requirements
		10.13.1 Directives
			10.13.1.1 Directive 93/42/EEC Regarding Medical Devices
			10.13.1.2 Directive 90/385/EEC Regarding Active Implantable Medical Devices
			10.13.1.3 Directive 98/79/EC Regarding Medical Devices for In Vitro Diagnosis
			10.13.1.4 Specific Regulations
	10.14 Clinical Applications of Orthopedic Implants
		10.14.1 Osteosynthesis
		10.14.2 Joint Replacement
		10.14.3 Nonconventional Modular Tumor Implants
		10.14.4 Spine Implants
	10.15 Marketed Products: An Update
		10.15.1 Medical Orthopedic Implants Market Segmentation
	10.16 Conclusions
	Abbreviations
	References
11 Biomaterials and Nanoparticles for Hyperthermia Therapy
	11.1 Introduction
		11.1.1 Hyperthermia: Historical Perspectives
		11.1.2 Basic Principles of Hyperthermia
			11.1.2.1 Physiology of Hyperthermia
			11.1.2.2 Mechanism of Hyperthermia Cytotoxicity
		11.1.3 Thermotolerance
		11.1.4 Human Body Temperature
	11.2 Factors Affecting Hyperthermia Treatments
	11.3 Classification of Hyperthermia
		11.3.1 Local Hyperthermia
		11.3.2 Regional-Deep Hyperthermia
		11.3.3 Whole-Body Hyperthermia
		11.3.4 Perfusion Therapy Hyperthermia
		11.3.5 Interstitial and Indocavity Hyperthermia
	11.4 Techniques Used for the Generation of Hyperthermia
		11.4.1 Microwave
		11.4.2 Radiofrequency
		11.4.3 Near Infrared
		11.4.4 Ultrasound
	11.5 Biomaterials and Nanoparticle in Hyperthermia Therapy
		11.5.1 Carbon Nanotubes for Hyperthermia Therapy
		11.5.2 Graphene and Graphene Oxide
		11.5.3 Gold Nanoshells
		11.5.4 Gold Nanorods
		11.5.5 Gold Nanoparticles
			11.5.5.1 Gold–Gold Sulfide Nanoparticles
			11.5.5.2 Hollow Gold Nanoshells
			11.5.5.3 Gold Colloidal Nanospheres
		11.5.6 Magnetic Nanoparticles
		11.5.7 Iron Oxide Nanoparticles
		11.5.8 Silica Nanoparticles
		11.5.9 Small Molecules Used in Hyperthermia
			11.5.9.1 IR780 Dyes
	11.6 Crosstalk on Various Application and Uses of Hyperthermia
		11.6.1 Hyperthermia in the Treatment of Brain Tumor
		11.6.2 Hyperthermia in the Treatment of Breast Cancer
		11.6.3 Cervical Cancer
		11.6.4 Melanoma
		11.6.5 Neck Cancer
		11.6.6 Hyperthermia in the Treatment of Arthritis
		11.6.7 Hyperthermia in the Treatment of Wounds
		11.6.8 Hyperthermia in the Treatment of Pain
	11.7 Hyperthermia Combined Therapy
		11.7.1 Hyperthermia Combined Chemotherapy
		11.7.2 Hyperthermia Combined Gene Therapy
		11.7.3 Hyperthermia Combined With Photodynamic Therapy
	11.8 Conclusions and Future Perspectives
	Abbreviations
	References
	Further reading
12 Hyaluronic Acid as an Emerging Technology Platform for Silencing RNA Delivery
	12.1 Hyaluronic Acid: Emerging Technology Platform
		12.1.1 History: A Brief Overview of Its Discovery
		12.1.2 Properties and Features
			12.1.2.1 Chemical Properties
			12.1.2.2 Physiological Properties
		12.1.3 Origin and Source of Hyaluronic Acid
		12.1.4 Physiological Actions of Hyaluronic Acid
		12.1.5 In Vivo Metabolism
		12.1.6 Formulation Strategies for Hyaluronic Acid-Based Nanoplatforms
			12.1.6.1 Desolvation Method
			12.1.6.2 Self-assembling Hyaluronic Acid Nanoparticles
	12.2 Introduction to RNA Interference
		12.2.1 Structure of Silencing RNA
		12.2.2 Silencing RNA Technology and Mechanism
		12.2.3 Problems in the Delivery of Silencing RNA
		12.2.4 Nanoparticles: The Salvager for the Silencing RNA Delivery
			12.2.4.1 Cationic Carrier Conjugation With Hyaluronic Acid: Solving the Compatibility Issue
	12.3 Hyaluronic Acid in Delivering Silencing RNA: Enhancing Target Specificity in Tumors
		12.3.1 Role in Colon Cancer
		12.3.2 Role in Ovarian Cancer
		12.3.3 Role in Breast Cancer
	12.4 Conclusion and Future Outlook
	Abbreviations
	References
	Further reading
13 Thiolated-Chitosan: A Novel Mucoadhesive Polymer for Better-Targeted Drug Delivery
	13.1 Introduction
	13.2 Polymers Used in Drug Delivery System
	13.3 Mucoadhesive Polymers: Emerging Class of Novel Polymers
		13.3.1 The Molecular Weight of the Polymer
		13.3.2 Polymer Chain Length
		13.3.3 Viscosity and Polymer Concentration
		13.3.4 The Degree of Cross-Linking and Degree of Swelling
		13.3.5 Flexibility of Polymer
		13.3.6 Hydrogen Bonding
	13.4 The Concept, Factors Affecting, and Theories of Mucoadhesion
		13.4.1 Electronic Theory
		13.4.2 Wetting Theory
		13.4.3 Cohesive Theory
		13.4.4 Adsorption Theory
		13.4.5 Diffusion Theory
		13.4.6 Mechanical Theory
	13.5 Chitosan as a Mucoadhesive Polymer
	13.6 Mucoadhesive Thiolated Chitosan: Next Generation Polymer for Drug Delivery
		13.6.1 Methods of Preparation
			13.6.1.1 Thiolation Using Thioglycolic Acid and Cysteine
			13.6.1.2 Thiolation Using 2-Iminothiolane (Traut’s Reagent)
			13.6.1.3 Thiolation Using 4 Mercaptobenzoic Acid
			13.6.1.4 Thiolation Using Thioethyl Amide
		13.6.2 Techniques to Prepare Micro- and Nanoparticulate Thiolated Chitosan
			13.6.2.1 Ionic Gelation
			13.6.2.2 Emulsification or Solvent Evaporation
			13.6.2.3 Radical Emulsion Polymerization
			13.6.2.4 Air Jet Milling
	13.7 Mucoadhesive Thiolated Chitosan: Effective Delivery Through Nanocarriers
		13.7.1 Nanoparticles
		13.7.2 Carbon Nanotubes
			13.7.2.1 Single-Walled Carbon Nanotubes
			13.7.2.2 Multiwalled Carbon Nanotubes
		13.7.3 Liposomes
		13.7.4 Niosomes
	13.8 Applications
		13.8.1 Thermosensitive Hydrogel Based on Thiolated Chitosan
		13.8.2 As Coating Polymer for Stents
		13.8.3 In Tissue Engineering
			13.8.3.1 Skin Tissue Engineering
			13.8.3.2 Bone Tissue Engineering
			13.8.3.3 Cartilage Tissue Engineering
		13.8.4 Matrix Tablet for Controlled Drug Delivery
	13.9 Conclusion
	Abbreviations
	References
14 Recent Advances and Challenges in Microneedle-Mediated Transdermal Protein and Peptide Drug Delivery
	14.1 Introduction to Transdermal Delivery of Protein and Peptides
	14.2 Mechanism of Skin-Based Microneedle Systems: Entry Into the Blood Circulation
	14.3 Skin Properties and Design of Microneedles: A Correlation
	14.4 Challenges in Microneedle-Mediated Protein Drug Delivery
		14.4.1 Skin Barrier
		14.4.2 Limitations of Existing Microneedle Treatment
		14.4.3 Physicochemical Instabilities of Protein Drugs
		14.4.4 Immunogenicity After Treatment
	14.5 Advances in Microneedle Technology in Protein Delivery
		14.5.1 Solid Microneedles Technology
		14.5.2 Coated Microneedles Technology
		14.5.3 Hollow Microneedles Technology
		14.5.4 Dissolving Microneedles Technology
		14.5.5 Hydrogel/Swellable Microneedles Technology
	14.6 Current Status of Protein and Peptide Containing Microneedles in Clinical Trials and Marketed Microneedle Products
	14.7 Conclusion
	Abbreviations
	References
	Further reading
15 Synthesis, Characterization, and Applications of Metal Nanoparticles
	15.1 Introduction
		15.1.1 Introduction to Metals: General Properties
		15.1.2 The Concept Behind Metallic Nanoparticles: Nanotechnology and Nanoscience
			15.1.2.1 Types of Nanoparticles: A Quick Look
				15.1.2.1.1 Inorganic Nanoparticles
				15.1.2.1.2 Polymeric Nanoparticles
					15.1.2.1.2.1 Solid Lipid Nanoparticles
					15.1.2.1.2.2 Liposomes
					15.1.2.1.2.3 Nanocrystals
					15.1.2.1.2.4 Nanotubes
					15.1.2.1.2.5 Dendrimers
		15.1.3 Advantages of Metallic Nanoparticles Over Polymeric Micro- and Nanostructures: Role in Pharmaceutical Systems
	15.2 General Methods in Metal Nanoparticles Synthesis
		15.2.1 Physical Approach
			15.2.1.1 Mechanical Methods
				15.2.1.1.1 Mechanical Ball Milling
				15.2.1.1.2 Mechanochemical Synthesis
			15.2.1.2 Vapor Methods
				15.2.1.2.1 Laser Ablation
				15.2.1.2.2 Exploding Wire
				15.2.1.2.3 Gas Evaporation
		15.2.2 Chemical Approach
		15.2.3 Biological Approach
			15.2.3.1 Nanoparticles via Actinomycetes
			15.2.3.2 Nanoparticles via Algae
			15.2.3.3 Nanoparticles via Bacteria
			15.2.3.4 Nanoparticles via Fungi
			15.2.3.5 Nanoparticles via Viruses
			15.2.3.6 Nanoparticles via Yeasts
			15.2.3.7 Nanoparticle via Plants
			15.2.3.8 Nanoparticles via Animal Tissues
				15.2.3.8.1 Silk Proteins (Fibroin and Sericin)
				15.2.3.8.2 Invertebrate
				15.2.3.8.3 Chitosan
	15.3 Synthesis of Gold Nanoparticles
	15.4 Synthesis of Silver Nanoparticles
	15.5 Synthesis of Iron Nanoparticles
	15.6 Synthesis of Zinc Oxide Nanoparticles
	15.7 Synthesis of Copper Nanoparticles
	15.8 Synthesis of Aluminum Nanoparticles
	15.9 Synthesis of Platinum Nanoparticles
	15.10 Synthesis of Ruthenium Nanoparticles
	15.11 Synthesis of Bimetallic Nanoparticles
	15.12 Synthesis of Metalloid and Nonmetal Nanoparticles
		15.12.1 Synthesis of Selenium Nanoparticles
		15.12.2 Synthesis of Sulfur Nanoparticles
	15.13 Surface Properties of Metal Nanoparticles
	15.14 Methods Used in Metal Nanoparticles Characterization
		15.14.1 Ultraviolet Visible Spectroscopy Studies and Plasmon Resonance
		15.14.2 Fourier Transforms Infrared Spectroscopy
		15.14.3 Scanning Electron Microscope
		15.14.4 Environmental Scanning Electron Microscope
		15.14.5 Transmission Electron Microscopy
		15.14.6 X-Ray Crystallography
		15.14.7 Energy-Dispersive X-Ray Spectroscopy
		15.14.8 Fluorescence Correlation Spectroscopy
		15.14.9 Surface-Enhanced Raman Spectroscopy
		15.14.10 Tip-Enhanced Raman Spectroscopy
		15.14.11 Zeta Potential
		15.14.12 Circular Dichroism
		15.14.13 Mass Spectroscopy
		15.14.14 Dynamic Light Scattering
		15.14.15 Scanning Tunneling Microscope
		15.14.16 Atomic-Force Microscopy
	15.15 Applications of Metal Nanoparticles
		15.15.1 Applications in Drug Delivery
		15.15.2 Application in Protein Delivery
		15.15.3 Application in Peptide Delivery
		15.15.4 Application in Gene Delivery
		15.15.5 Application in Tissue Engineering
		15.15.6 Application in Enzymology
		15.15.7 Application in Surface Coating of Nanoparticles
		15.15.8 Application in Biosensing Devices
		15.15.9 Application in Diagnostics
		15.15.10 Application in Theranostics
		15.15.11 Other Application
			15.15.11.1 Application in Cosmetics
			15.15.11.2 Application of Au Nanoparticle–Based Molecular Imaging
			15.15.11.3 Application in Wound Dressings
	15.16 Future Potential of Metallic Nanoparticles: Emerging Area of Biomedical Sciences
	Conclusion
	Abbreviations
	References
	Further Reading
16 Functionalized Carbon Nanotubes for Protein, Peptide, and Gene Delivery
	16.1 Introduction to Nanotechnology
	16.2 Carbon Nanotubes: Structure and Classification
	16.3 Synthesis and Purification of Carbon Nanotubes
		16.3.1 Carbon Arc-Discharge Technique
		16.3.2 Laser-Ablation Technique
		16.3.3 Chemical Vapor Deposition Technique
		16.3.4 Purification of Carbon Nanotubes
	16.4 Functionalization of Carbon Nanotubes
		16.4.1 Covalent Functionalization
		16.4.2 Noncovalent Functionalization
	16.5 Functionalization of Carbon Nanotube With Protein, Peptide, DNA, and SiRNA
	16.6 Role of Peptides in Cancer Management
	16.7 Carbon Nanotube–Mediated Peptide and Vaccine Delivery
	16.8 Carbon Nanotube–Mediated Gene Delivery
	16.9 Cellular Uptake and Cell Penetration Mechanism of Carbon Nanotubes
	16.10 Toxicity Consideration of Carbon Nanotubes
	16.11 Future Scope and Conclusion
	References
17 Surface Modifications of Biomaterials and Their Implication on Biocompatibility
	17.1 Introduction to Biomaterials
	17.2 Compatibility of the Biomaterial With Biological Surfaces: Challenges and Opportunity
		17.2.1 The Need for Surface Modification of Biomaterials
		17.2.2 Nonfouling Surfaces
	17.3 Approaches for Surface Modification and Influences on Biocompatibility
		17.3.1 Cationization
		17.3.2 Carboxylation
		17.3.3 Polyethylene Oxide and Derivatives
		17.3.4 Polyoxazoline Conjugation
		17.3.5 Albumin coating
		17.3.6 Phospholipidic Coating
		17.3.7 Chitosan Coating
	17.4 Immobilization of Biomolecule on a Surface of Biomaterials
		17.4.1 Physical Adsorption
		17.4.2 Chemical Bonding With Biomolecules
		17.4.3 Physical Entrapment
		17.4.4 Chemical Modification
	17.5 Techniques to Assess the Biocompatibility of Polymers
		17.5.1 In Vitro Testing
		17.5.2 Ex Vivo Testing
			17.5.2.1 Cytotoxicity Test
			17.5.2.2 Hemocompatibility
		17.5.3 In Vivo Techniques to Assess the Biocompatibility of Polymers
			17.5.3.1 Alanine Aminotransferase
			17.5.3.2 Alanine Transaminase
			17.5.3.3 Blood Urea Nitrogen
	17.6 Effect of Surface Modification of Biomaterials for Biocompatibility
		17.6.1 Influence of Protein-Modified Surface
		17.6.2 Influence of Surface Functional Groups on Cellular Responses
		17.6.3 Carboxyl (–COOH) Functional Group-Bearing Surface
		17.6.4 Hydroxyl (–OH) Functional Group–Coated Surfaces
		17.6.5 Amine (–NH2) Functional Group-Rich Surfaces
		17.6.6 Methyl (–CH3) Functional Group-Bearing Surfaces
		17.6.7 Surfaces With Mixed Functionality
	17.7 Conclusion
	References
Index
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